DNA硫代磷酸酯修饰影响整体转录反应并保护DNA免受双链断裂。

Gan Rui, Wu Xiaolin, He Wei, Liu Zhenhua, Wu Shuangju, Chen Chao, Chen Si, Xiang Qianrong, Deng Zixin, Liang Dequan, Chen Shi, Wang Lianrong

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.

1] Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China [2] Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

Sci Rep. 2014 Oct 16;4:6642. doi: 10.1038/srep06642.

The modification of DNA by phosphorothioate (PT) occurs when the non-bridging oxygen in the sugar-phosphate backbone of DNA is replaced with sulfur. This DNA backbone modification was recently discovered and is governed by the dndABCDE genes in a diverse group of bacteria and archaea. However, the biological function of DNA PT modifications is poorly understood. In this study, we employed the RNA-seq analysis to characterize the global transcriptional changes in response to PT modifications. Our results show that DNA without PT protection is susceptible to DNA damage caused by the dndFGHI gene products. The DNA double-stranded breaks then trigger the SOS response, cell filamentation and prophage induction. Heterologous expression of dndBCDE conferring DNA PT modifications at GPSA and GPST prevented the damage in Salmonella enterica. Our data provide insights into the physiological role of the DNA PT system.

当DNA糖磷酸骨架中的非桥连氧被硫取代时，就会发生硫代磷酸酯（PT）对DNA的修饰。这种DNA骨架修饰是最近发现的，并且在多种细菌和古细菌中受dndABCDE基因控制。然而，人们对DNA PT修饰的生物学功能了解甚少。在本研究中，我们采用RNA测序分析来表征响应PT修饰的全局转录变化。我们的结果表明，没有PT保护的DNA易受dndFGHI基因产物引起的DNA损伤。DNA双链断裂随后触发SOS反应、细胞丝化和原噬菌体诱导。在GPSA和GPST处赋予DNA PT修饰的dndBCDE的异源表达可防止肠炎沙门氏菌受到损伤。我们的数据为DNA PT系统的生理作用提供了见解。